This project is designed to evaluate a series of 24 oxazolidines synthesized from ephedrine and its stereoisomers for their potential use as prodrugs using pharmacological and plasma hydrolysis models. These compounds were chosen because in each case, the (-)ephedrine isomer has been shown to have ephedrine-like pharmacological activity in rats. Earlier investigators have suggested the possible use of oxazolidines derived from ephedrine as prodrugs. They based their hypothesis upon the observations that these compounds readily hydrolyze in aqueous media to release ephedrine, are more lipophilic than ephedrine, and readily permeate human epithelial tissue. Such prodrugs could possible find use in bronchial inhalants and nasal sprays for treatment of the symptoms of bronchial asthma, colds and allergies. In the study, we plan to further test this hypothesis by examining the kinetics of hydrolysis of these compounds in human plasma and continue pharmacological testing for ephedrine-like activity in three animal models. The models to be used are hyperthermia, anorexia, and increased locomotor activity in rats. Ephedrine has been shown to give a distinct response in each of these models. Several oxazolidines have also been shown to be active in these models. Octanol-water partition coefficients will be measured or estimated by calculation for those compounds whose coefficients have not been measured. In vivo pharmacokinetic models will be developed later based on the results of the plasma hydrolysis studies. These will be submitted as a separate proposal.